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C Gordon

Publications and source records attributed to C Gordon.

At least 91 records · Page 5Linked to original sources
PubMed1999

The association of socio-economic status, race, psychosocial factors and outcome in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the relationship between socio-economic status, race, psychosocial factors and outcome in patients with systemic lupus erythematosus (SLE). METHODS: One hundred and ninety-five patients with SLE were studied at two centres in the UK (London and Birmingham). Information about sociodemographics, income, employment status, social support and satisfaction with care was obtained. Outcomes were assessed by end-organ damage, disease activity and employment status. RESULTS: Non-Caucasian race, longer disease duration, higher disease activity and lower level of education were associated with more organ damage in SLE. More satisfaction with access to care and interpersonal aspects of care, but less satisfaction with time spent with doctors, were also associated with more damage. Very long disease duration was associated with higher disease activity. Patients with higher disease activity, lower level of education and from the Birmingham centre were more likely not to be working due to their lupus. CONCLUSION: Race and socio-economic status, as well as clinical and psychosocial factors, determine outcome in SLE.

Adult↗
PubMed1999

A cell line-based neutralization assay for primary human immunodeficiency virus type 1 isolates that use either the CCR5 or the CXCR4 coreceptor.

We describe here a cell line-based assay for the evaluation of human immunodeficiency virus type 1 (HIV-1) neutralization. The assay is based on CEM.NKR cells, transfected to express the HIV-1 coreceptor CCR5 to supplement the endogenous expression of CD4 and the CXCR4 coreceptor. The resulting CEM.NKR-CCR5 cells efficiently replicate primary HIV-1 isolates of both R5 and X4 phenotypes. A comparison of the CEM.NKR-CCR5 cells with mitogen-activated peripheral blood mononuclear cells (PBMC) in neutralization assays with sera from HIV-1-infected individuals or specific anti-HIV-1 monoclonal antibodies shows that the sensitivity of HIV-1 neutralization is similar in the two cell types. The CEM.NKR-CCR5 cell assay, however, is more convenient to perform and eliminates the donor-to-donor variation in HIV-1 replication efficiency, which is one of the principal drawbacks of the PBMC-based neutralization assay. We suggest that this new assay is suitable for the general measurement of HIV-1 neutralization by antibodies.

CD4 Antigens↗
PubMed1999

The CC-chemokine RANTES increases the attachment of human immunodeficiency virus type 1 to target cells via glycosaminoglycans and also activates a signal transduction pathway that enhances viral infectivity.

We have studied the mechanisms by which the CC-chemokine RANTES can enhance the infectivities of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses, when present at concentrations in excess of 500 ng/ml in vitro. Understanding the underlying mechanisms might throw light on fundamental processes of viral infection, in particular for HIV-1. Our principal findings are twofold: firstly, that oligomers of RANTES can cross-link enveloped viruses, including HIV-1, to cells via glycosaminoglycans (GAGs) present on the membranes of both virions and cells; secondly, that oligomers of RANTES interact with cell-surface GAGs to transduce a herbimycin A-sensitive signal which, over a period of several hours, renders the cells more permissive to infection by several viruses, including HIV-1. The enhancement mechanisms require that RANTES oligomerize either in solution or following binding to GAGs, since no viral infectivity enhancement is observed with a mutant form of the RANTES molecule that contains a single-amino-acid change (glutamic acid to serine at position 66) which abrogates oligomerization.

Animals↗
PubMed1999

Defects in components of the proteasome enhance transcriptional silencing at fission yeast centromeres and impair chromosome segregation.

Fission yeast centromeres are transcriptionally silent and form a heterochromatin-like structure essential for normal centromere function; this appears analogous to heterochromatin and position effect variegation in other eukaryotes. Conditional mutations in three genes designated cep (centromere enhancer of position effect) were found to enhance transcriptional silencing within centromeres. Cloning of the cep1(+) and cep2(+) genes by functional complementation revealed that they are identical to the previously described genes pad1(+) and mts2(+), respectively, which both encode subunits of the proteasome 19S cap. Like Mts2 and Mts4, epitope-tagged Cep1/Pad1 localizes to or near the nuclear envelope throughout the cell cycle. The cep mutants display a range of phenotypes depending on the temperature. Silencing within the central domain of centromeres is increased at 36 degrees C. This suggests that the proteasome is involved in regulating silencing and thus centromeric chromatin architecture, possibly by lowering the level of some chromatin-associated protein by ubiquitin-dependent degradation. This is the first report of defective proteasome function affecting heterochromatin-mediated transcriptional silencing. At 36 and 32 degrees C, the cep mutants lose chromosomes at an elevated rate, and at 18 degrees C, the mutants are cryosensitive for growth. Cytological analysis at 18 degrees C revealed a defect in sister chromatid separation while other mitotic events occurred normally, indicating that cep mutations might interfere specifically with the degradation of inhibitor(s) of sister chromatid separation. These observations suggest that 19S subunits confer a level of substrate specificity on the proteasome and raise the possibility of a link between components involved in centromere architecture and sister chromatid cohesion.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1999

The A-G polymorphism in exon 1 of the CTLA-4 gene is not associated with systemic lupus erythematosus.

OBJECTIVES: Factors contributing to the development of systemic lupus erythematosus (SLE) remain largely unknown although are likely to include both environmental and genetic components. Studies on murine lupus have indicated a role for an antibody that blocks binding of cytotoxic T lymphocyte associated-4 (CTLA-4) to B7 on antigen presenting cells in the treatment of disease, suggesting that CTLA-4 may play an important part in the disease process. This study, therefore, investigated the frequency of a previously described A-G polymorphism in exon 1 of the CTLA-4 gene, the G allele of which has shown to be associated with both Graves' disease and type I diabetes, to determine whether this polymorphism was playing a part in the development of SLE. METHODS: One hundred and twenty six SLE patients and 363 control subjects were genotyped for the A-G polymorphism in exon 1 of the CTLA-4 gene. Target DNA was amplified using the polymerase chain reaction and the resulting product was digested using the BbvI restriction enzyme. RESULTS: No differences in allele or genotype frequencies were observed between patients with SLE and control subjects. CONCLUSION: These data suggest that the A-G polymorphism in exon 1 of the CTLA-4 gene does not play a part in the genetic susceptibility to the development of SLE.

Abatacept↗
PubMed1999

Quality of life and economic evaluation in SLE clinical trials.

Outcome in SLE patients should include assessment of disease activity and chronic damage and also measurement of health-related quality of life and the economic impact of the disease. This paper reviews the methods available for doing this and the results of existing studies in SLE patients.

Anxiety↗
PubMed1999

Factors involved in the pathogenesis of neutrophilic vasculitis in MRL/Mp-lpr/lpr mice: a model for human microscopic angiitis.

Anti-neutrophil cytoplasm antibodies (ANCA) directed against myeloperoxidase (MPO) are detected in patients with microscopic angiitis. Human MPO autoantibodies stimulate neutrophil degranulation in vitro and are thought to be pathogenic. We have previously shown that MRL-lpr mice with MPO autoantibodies have a higher incidence of vasculitis than their seronegative littermates. The aim of the present study is to determine the relationship between MPO autoantibodies and microscopic angiitis. The neutrophil binding properties of anti-MPO monoclonal antibodies (mAbs) from MRL-lpr mice were tested using murine heterophils (neutrophils) present in blood and induced peritoneal exudates. MRL anti-MPO mAbs selectively bind activated neutrophils which express MPO in vitro. The pathogenicity of an IgG2b anti-MPO mAb, C6, was investigated in vivo. Anti-MPO mAb, C6 was administered to young MRL mice which had been primed with exogenous TNF alpha to induce neutrophil activation and expression of MPO. Neutrophilic vasculitis similar to microscopic angiitis occurred in 33% of MRL mice which had been treated with anti-MPO mAb. The lesions were mainly restricted to sites of previous endothelial insult which suggests an active role for injured endothelium in this pathology.

Animals↗
PubMed1999

An international perspective on the well being and health care costs for patients with systemic lupus erythematosus. Tri-Nation Study Group.

OBJECTIVE: To compare health care expenditure and health status for patients with systemic lupus erythematosus (SLE) between nations with distinct mechanisms for funding and delivering health care services. METHODS: Seven hundred eight patients with SLE from 2 centers in each of 3 countries (Canada 229, United States 268, United Kingdom 211) underwent physician assessment of disease activity and damage and reported on physical and psychosocial well being, satisfaction, social support, and health resource utilization. To compare overall utilization, constant prices (1997 Canadian dollars) were applied across countries for each service, enabling diverse resources to be collapsed into a single expression. RESULTS: After adjusting for important patient covariates, Canadian, compared to American and British patients, reported significantly superior health status in 3 of 8 Medical Outcome Survey Short Form-36 (SF-36) subscales, the SF-36 physical component summary score, and the visual analog scale of general health status. There was no consistent trend in patient satisfaction. Overall annual resource utilization did not vary significantly, with mean annual per patient expenditures (adjusted for demographics, disease duration, activity, damage, social support, health status, patient satisfaction, and age and sex adjusted country-specific SF-36 general population norms) totalling $4853, $5285, and $4760 for Canada, US, and the UK, respectively. However, within each resource category, differences were observed. Canadians saw more specialists than the British, the British more generalists. Canadians and Americans were more frequent users of the emergency room; Americans of laboratory/imaging procedures. Canadians had higher hospital costs than Americans. CONCLUSION: After adjustment, Canadian patients reported better well being than their counterparts. Despite considerable differences in the mechanisms of health care funding and service mixture, overall resource utilization did not vary significantly between the countries, although there was a trend towards more intense use of inpatient services in Canada and outpatient services in the United States.

Adult↗
PubMed1999

Associates of health status in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the health status of patients with systemic lupus erythematosus (SLE) and to identify the associations of this domain. METHODS: One hundred ninety-five consecutively attending patients with SLE were studied at 2 centers. Health status was measured by 8 composite scales of the Medical Outcomes Study Short Form 36 (SF-36). The mean scores for each subscale of the SF-36 for patients with SLE were compared to those of a healthy population. The effect of patients' age, sex, ethnic origin, marital status, education level, disease duration, disease activity (assessed by the Systemic Lupus Activity Measure), end organ damage (assessed by the Systemic Lupus International Coordinating Clinics/American College of Rheumatology Damage Index), social support (using the Interpersonal Support Evaluation List), and patients' satisfaction with medical care (using the Patient Satisfaction Questionnaire) on each SF-36 subscale was determined. Student's unpaired t test and multiple regression analysis were applied for statistical analysis. RESULTS: Patients with SLE had significantly lower scores in each subscale of the SF-36 compared to a control population. Higher disease activity was associated with worse physical function, role-physical, bodily pain, general health, vitality, and social function. Greater social support was associated with higher scores in physical function, bodily pain, general health, vitality, social function, role-emotional, and mental health. Increasing total end organ damage determined worse physical function and general health. Higher patient general satisfaction with care was associated with better general health. CONCLUSION: The health status of patients with SLE may be improved by increasing patients' social support and satisfaction with health care, as well as controlling SLE disease activity and preventing organ damage.

Adolescent↗
PubMed1999

Randomized clinical trials and longitudinal observational studies in systemic lupus erythematosus: consensus on a preliminary core set of outcome domains.

The OMERACT module on systemic lupus erythematosus (SLE) dealt with the definition of preliminary core sets of outcome domains for randomized clinical trials (RCT) and longitudinal observational studies (LOS). After lectures introducing the problems and addressing the key issues, 6 discussion groups, 3 each for LOS and RCT, discussed and weighted more than a dozen possible items for use as outcome domains. The means of the respective 3 groups were calculated. For both RCT and LOS the same outcome domains received more than 10 of a total maximum of 100 points: disease activity, health related quality of life (HRQOL), damage, and toxicity/adverse events. However, the weights for HRQOL and damage were different for LOS and RCT. A final vote led to the acceptance of these 4 variables as a preliminary core set for outcome in SLE by more than 80% of the participants. This core set will allow for improved design, performance, and evaluation of future studies in SLE. However, a number of domains not included in the core set were regarded as important for further analysis and research.

Decision Making↗
PubMed1998

Localization of the 26S proteasome during mitosis and meiosis in fission yeast.

The 26S proteasome is a large multisubunit complex involved in degrading both cytoplasmic and nuclear proteins. We have investigated the localization of this complex in the fission yeast, Schizosaccharomyces pombe. Immunofluorescence microscopy shows a striking localization pattern whereby the proteasome is found predominantly at the nuclear periphery, both in interphase and throughout mitosis. Electron microscopic analysis revealed a concentration of label near the inner side of the nuclear envelope. The localization of green fluorescent protein (GFP)-tagged 26S proteasomes was analyzed in live cells during mitosis and meiosis. Throughout mitosis the proteasome remained predominantly at the nuclear periphery. During meiosis the proteasome was found to undergo dramatic changes in its localization. Throughout the first meiotic division, the signal is more dispersed over the nucleus. During meiosis II, there was a dramatic re-localization, and the signal became restricted to the area between the separating DNA until the end of meiosis when the signal dispersed before returning to the nuclear periphery during spore formation. These findings strongly imply that the nuclear periphery is a major site of protein degradation in fission yeast both in interphase and throughout mitosis. Furthermore they raise interesting questions as to the spatial organization of protein degradation during meiosis.

Base Sequence↗
PubMed1998

The Pad1+ gene encodes a subunit of the 26 S proteasome in fission yeast.

We have isolated a fission yeast mutant, mts5-1, in a screen for mutations that confer both methyl 2-benzimidazolecarbamate resistance (MBCR) and temperature sensitivity (ts) on Schizosaccharomyces pombe. This screen has previously isolated mutations in the 26 S proteasome subunits Mts2, Mts3, and Mts4. We show that the mutation in the mts5-1 strain occurs in the pad1(+) gene. pad1(+) was originally isolated on a multicopy plasmid that was capable of conferring staurosporine resistance on a wild type strain. mts5-1/pad1-1 has a similar phenotype to 26 S proteasome mutants previously isolated in the same screen and we show that Pad1 interacts genetically with two of these subunits, Mts3 and Mts4. In this study we describe the identification of Pad1 as a subunit of the 26 S proteasome in fission yeast.

Amino Acid Sequence↗
PubMed1998

Serum sex-hormone-binding globulin is related to hepatic and peripheral insulin sensitivity but not to beta-cell function in men and women with Type 2 diabetes mellitus.

This study examined the relationship of hepatic and peripheral insulin sensitivity and beta-cell secretory function with serum sex hormone-binding globulin (SHBG) in men and women with Type 2 diabetes mellitus (DM). Fasting insulin, glucose and SHBG were measured in 58 Type 2 diabetic patients of both sexes (36 men) who were on diet treatment only and terms for insulin sensitivity and beta-cell secretion obtained by modelling. There was no significant difference in SHBG between men and women despite similar degree of obesity. SHBG was positively correlated (r = 0.41, p < 0.01) to hepatic insulin sensitivity derived from mathematical modelling of fasting glucose and insulin data using the homeostasis assessment model (HOMA). This relationship was independent of gender (men, r = 0.48, p < 0.01; women, r = 0.45, p < 0.05). Fasting insulin correlated negatively with SHBG in men (r = -0.34, p < 0.05). There were also significant negative correlations between SHBG and either plasma glucose (r = -0.29, p < 0.05) or body mass index (r = -0.34, p < 0.05). SHBG did not correlate with HOMA-modelled beta-cell function. In a multiple regression analysis, SHBG was independently correlated only with insulin sensitivity (p < 0.05). Further studies in 15 of the diabetic patients (11 men), showed a significant positive correlation (r = 0.52, p < 0.05) between SHBG and peripheral insulin sensitivity derived by continuous infusion of glucose with model assessment (CIGMA) but not between SHBG and CIGMA-modelled beta-cell function. These results indicate that both hepatic and peripheral insulin sensitivity are similarly related to serum SHBG in Type 2 diabetes of both sexes. The sex-difference in SHBG was abolished in the patients.

Diabetes Mellitus, Type 2↗